Jan Akervall1, Sirisha Nandalur2, Jacob Zhang3, Chao-Nan Qian3, Neal Goldstein4, Paulina Gyllerup5, Ylva Gardinger5, Jens Alm5, Katarina Lorenc5, Karolina Nilsson5, James Resau3, George Wilson2, Bin Teh3. 1. Department of Otolaryngology, Head and Neck Surgery, Surgical Services, Oakland University - William Beaumont School of Medicine, Royal Oak, MI, USA; Department of Otolaryngology, Head and Neck Surgery, University Hospital, Lund, Sweden. Electronic address: jan.akervall@beaumont.edu. 2. Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI, USA. 3. Van Andel Institute, Grand Rapids, MI, USA. 4. Department of Pathology, William Beaumont Hospital, Royal Oak, MI, USA. 5. Van Andel Institute, Grand Rapids, MI, USA; Department of Otolaryngology, Head and Neck Surgery, University Hospital, Lund, Sweden.
Abstract
PURPOSE: Global gene expression analysis was performed on pre-treatment biopsies from patients with squamous cell carcinoma of the head and neck (SCCHN) to discover biomarkers that can predict outcome of radiation based therapy. METHODS: We initially evaluated RNA expression using cDNA microarray analysis of 38 patients that received radiotherapy (RT). The five strongest candidates (VEGF, BCL-2, CLAUDIN-4, YAP-1 and c-MET) were then analysed in pre-treatment biopsies in a second group of 86 patients who received radiation based treatment using immunohistochemical staining (IHC), prepared by tissue microarray. RESULTS: In the first population, 13 of 38 (34%) had no (NR) or partial response (PR) to RT. cDNA microarrays revealed 60 genes that were linked to response to therapy. In the second series, 12 of 86 patients (14%) experienced NR or PR to CRT. Cause specific survival (CSS) and recurrence free survival (RFS) at 2 years was 85% and 90% and at 3 years 81% and 84%, respectively. Biomarkers predictive for NR/PR were increased expression of vascular endothelial growth factor (VEGF) (p=0.02), Yes-associated protein (YAP-1) (p<0.01), CLAUDIN-4 (p<0.01), c-MET (p<0.01) and BCL-2 (p=0.02). Biomarkers predictive of poor RFS were YAP-1 (p=0.01) and BCL-2 (p<0.01). Biomarkers predictive of poor CSS were YAP-1 (p=0.04), VEGF (p=0.03) and CLAUDIN-4 (p=0.03). Furthermore, when YAP-1 and c-MET expression levels were combined the prediction of radio-resistance was increased. CONCLUSION: All five biomarkers were predictive of poor response to radiation based therapy. In particular, YAP-1 and c-MET have synergistic power and could be used to make treatment decisions.
PURPOSE: Global gene expression analysis was performed on pre-treatment biopsies from patients with squamous cell carcinoma of the head and neck (SCCHN) to discover biomarkers that can predict outcome of radiation based therapy. METHODS: We initially evaluated RNA expression using cDNA microarray analysis of 38 patients that received radiotherapy (RT). The five strongest candidates (VEGF, BCL-2, CLAUDIN-4, YAP-1 and c-MET) were then analysed in pre-treatment biopsies in a second group of 86 patients who received radiation based treatment using immunohistochemical staining (IHC), prepared by tissue microarray. RESULTS: In the first population, 13 of 38 (34%) had no (NR) or partial response (PR) to RT. cDNA microarrays revealed 60 genes that were linked to response to therapy. In the second series, 12 of 86 patients (14%) experienced NR or PR to CRT. Cause specific survival (CSS) and recurrence free survival (RFS) at 2 years was 85% and 90% and at 3 years 81% and 84%, respectively. Biomarkers predictive for NR/PR were increased expression of vascular endothelial growth factor (VEGF) (p=0.02), Yes-associated protein (YAP-1) (p<0.01), CLAUDIN-4 (p<0.01), c-MET (p<0.01) and BCL-2 (p=0.02). Biomarkers predictive of poor RFS were YAP-1 (p=0.01) and BCL-2 (p<0.01). Biomarkers predictive of poor CSS were YAP-1 (p=0.04), VEGF (p=0.03) and CLAUDIN-4 (p=0.03). Furthermore, when YAP-1 and c-MET expression levels were combined the prediction of radio-resistance was increased. CONCLUSION: All five biomarkers were predictive of poor response to radiation based therapy. In particular, YAP-1 and c-MET have synergistic power and could be used to make treatment decisions.
Authors: Mathias Fiedler; Florian Weber; Matthias G Hautmann; Frank Haubner; Torsten E Reichert; Christoph Klingelhöffer; Stephan Schreml; Johannes K Meier; Arndt Hartmann; Tobias Ettl Journal: Clin Oral Investig Date: 2017-03-18 Impact factor: 3.573